Osteopontin: A Biomarker to Predict the Outcome of Inflammatory Heart Disease

Abstract

Inflammatory processes of the heart are often induced by viruses. Although most acute virus-induced myocarditis quickly resolves, some patients develop chronic myocarditis resulting in a considerable disruption of the myocardial matrix network, finally leading to cardiac dysfunction. The death of cardiomyocytes due to virus replication is followed by the attraction of macrophages and T cells to the sites of cardiac damage. Ongoing inflammation is usually suppressed by interleukin-10 and transforming growth factor-beta production, thus activating myofibroblasts and secretion of extracellular matrix proteins like collagen type I. Also, osteopontin (OPN), a matricellular protein with cytokine-like properties, is critically involved in inflammatory pathways and can modulate the cell biology of cardiac repair. In our model of coxsackievirus B3-induced myocarditis, we have shown that increased early OPN expression in macrophages is a determinant of fibrosis and enhanced cardiac remodeling. OPN was not found to influence the efficacy of the antiviral immune response. Also, in patients with acute and chronic myocarditis, but not in patients with end-stage dilated cardiomyopathy, we found a high OPN expression in macrophages, indicating active inflammatory processes. Thus cardiac OPN expression might be considered as a biomarker indicating ongoing cardiac inflammation preceding fibrosis and remodeling of the heart.